Elevator music as a tool for the quantitative characterization of reward.

While certain musical genres and songs are widely popular, there is still large variability in the music that individuals find rewarding or emotional, even among those with a similar musical enculturation. Interestingly, there is one Western genre that is intended to attract minimal attention and evoke a mild emotional response: elevator music. In a series of behavioral experiments, we show that elevator music consistently elicits low pleasure and surprise. Participants reported elevator music as being less pleasurable than music from popular genres, even when participants did not regularly listen to the comparison genre. Participants reported elevator music to be familiar even when they had not explicitly heard the presented song before. Computational and behavioral measures of surprisal showed that elevator music was less surprising, and thus more predictable, than other well-known genres. Elevator music covers of popular songs were rated as less pleasurable, surprising, and arousing than their original counterparts. Finally, we used elevator music as a control for self-selected rewarding songs in a proof-of-concept physiological (electrodermal activity and piloerection) experiment. Our results suggest that elevator music elicits low emotional responses consistently across Western music listeners, making it a unique control stimulus for studying musical novelty, pleasure, and surprise.

Clinical Validation of the Canada Lymph Node Score for Endobronchial Ultrasound.

BACKGROUND: The Canada Lymph Node Score (CLNS) uses 4 sonographic criteria to predict the risk of malignancy in lymph nodes during endobronchial ultrasound. The CLNS may play a role in identifying targets for biopsy or rebiopsy during invasive mediastinal staging for lung cancer. However the CLNS has not yet been prospectively validated in routine clinical practice. METHODS: CLNSs for each lymph node biopsied during endobronchial ultrasound were prospectively captured for 1 year (2019). The CLNS and the presence of malignancy in each node were compared. Univariate binary logistic regression was completed for each ultrasonographic feature and multivariate logistic regression model. RESULTS: CLNSs and diagnostic pathology results were available for 367 lymph nodes. Incidence of malignancy increased with higher scores. Scores ≥ 3 were significantly associated with malignancy (specificity, 84.4%; positive likelihood ratio, 4.0). Area under the curve was 0.76, indicating a good ability of the model to predict presence or absence of malignancy. Nodes scoring < 2 and negative on computed tomography and positron emission tomography were malignant in 10.1%. CONCLUSIONS: The CLNS correlates with the presence or absence of malignancy in thoracic lymph nodes and may serve as an adjunct to currently available methods of invasive and noninvasive mediastinal staging. The CLNS may be most helpful in selecting which nondiagnostic lymph nodes require rebiopsy. There is a significant risk of a false-negative result even with a score of 0, and using a combination of low CLNSs and negative conventional radiology to obviate the need for any initial biopsy remains to be studied in prospective trials.

Rad53 arrests leading and lagging strand DNA synthesis via distinct mechanisms in response to DNA replication stress.

DNA replication stress threatens ordinary DNA synthesis. The evolutionarily conserved DNA replication stress response pathway involves sensor kinase Mec1/ATR, adaptor protein Mrc1/Claspin, and effector kinase Rad53/Chk1, which spurs a host of changes to stabilize replication forks and maintain genome integrity. DNA replication forks consist of largely distinct sets of proteins at leading and lagging strands that function autonomously in DNA synthesis in vitro. In this article, we discuss eSPAN and BrdU-IP-ssSeq, strand-specific sequencing technologies that permit analysis of protein localization and DNA synthesis at individual strands in budding yeast. Using these approaches, we show that under replication stress Rad53 stalls DNA synthesis on both leading and lagging strands. On lagging strands, it stimulates PCNA unloading, and on leading strands, it attenuates the replication function of Mrc1-Tof1. We propose that in doing so, Rad53 couples leading and lagging strand DNA synthesis during replication stress, thereby preventing the emergence of harmful ssDNA.

Stable inheritance of H3.3-containing nucleosomes during mitotic cell divisions.

Newly synthesized H3.1 and H3.3 histones are assembled into nucleosomes by different histone chaperones in replication-coupled and replication-independent pathways, respectively. However, it is not clear how parental H3.3 molecules are transferred following DNA replication, especially when compared to H3.1. Here, by monitoring parental H3.1- and H3.3-SNAP signals, we show that parental H3.3, like H3.1, are stably transferred into daughter cells. Moreover, Mcm2-Pola1 and Pole3-Pole4, two pathways involved in parental histone transfer based upon the analysis of modifications on parental histones, participate in the transfer of both H3.1 and H3.3 following DNA replication. Lastly, we found that Mcm2, Pole3 and Pole4 mutants defective in parental histone transfer show defects in chromosome segregation. These results indicate that in contrast to deposition of newly synthesized H3.1 and H3.3, transfer of parental H3.1 and H3.3 is mediated by these shared mechanisms, which contributes to epigenetic memory of gene expression and maintenance of genome stability.

Streptococcus mutans isolated from children with severe-early childhood caries form higher levels of persisters.

OBJECTIVES: Dental caries is the most common chronic infectious disease in children. Streptococcus mutans, the main cariogenic bacterial species, produces persisters, nongrowing dormant variants of regular cells associated with chronicity of diseases. We hypothesized that the recurrent nature of caries, particularly within populations with high-caries risk, is due partly to specific phenotypic features of S. mutans such as its ability to form persisters. We aimed to investigate the genotypic and phenotypic differences between the S. mutans from children with severe early-childhood caries (S-ECC) and those without caries. METHODS: S. mutans from plaque samples of caries-free (CF) and S-ECC children were tested for their ability to adapt to a lethal pH in an acid tolerance response assay. The persister levels of S. mutans isolates was quantified in both groups. RESULTS: S. mutanswas identified in all 23 S-ECC but only 6 of the 21 CF subjects. In most subjects, only one dominant S. mutans genotype was detected. No statistically significant differences in the mean survival percentage of S. mutans were observed between the two groups at a lethal pH of 3.5. However, the dominant genotype within a particular S-ECC subject exhibited a higher percentage of cell survival compared to those in the CF group. In S-ECC patients, S. mutans isolates displayed a ∼15-fold higher persistence phenotype than S. mutans isolates from CF patients. CONCLUSIONS: The ability of S. mutans to produce high levels of persisters may contribute to part of an individual's ability to control caries disease activity and recurrent lesions.

Complete Genome Sequence of Streptococcus mutans Strain LAB761, Which Harbors Several Bacteriocin Loci, Isolated from a Caries-Active Child in Canada.

Streptococcus mutans LAB761 has been isolated from dental plaque collected from a child with severe caries. We report here the complete genome sequence of S. mutans strain LAB761, which has a chromosome of 2.0 Mb. The genome sequence reported herein contains several loci encoding double-glycine-motif peptides and lantibiotic and nonlantibiotic bacteriocins.

Stress Odorant Sensory Response Dysfunction in Drosophila Fragile X Syndrome Mutants.

Sensory processing dysfunction (SPD) is present in most patients with intellectual disability (ID) and autism spectrum disorder (ASD). Silencing expression of the Fragile X mental retardation 1 (FMR1) gene leads to Fragile X syndrome (FXS), the most common single gene cause of ID and ASD. Drosophila have a highly conserved FMR1 ortholog, dfmr1. dfmr1 mutants display cognitive and social defects reminiscent of symptoms seen in individuals with FXS. We utilized a robust behavioral assay for sensory processing of the Drosophila stress odorant (dSO) to gain a better understanding of the molecular basis of SPD in FXS. Here, we show that dfmr1 mutant flies present significant defects in dSO response. We found that dfmr1 expression in mushroom bodies is required for dSO processing. We also show that cyclic adenosine monophosphate (cAMP) signaling via PKA is activated after exposure to dSO and that several drugs regulating both cAMP and cyclic guanosine monophosphate (cGMP) levels significantly improved defects in dSO processing in dfmr1 mutant flies.